Candidate: The Candidate's long-term career objective is to advance the scientific understanding and clinical care of individuals with multiple sclerosis (MS) and other neurological disorders through the development and application of integrated functional and structural neuroimaging methods. She has formal training and experience in clinical research, and has acquired basic concepts and techniques of clinical neuroimaging research. Her major five-year career goal is to develop expertise in the use of functional magnetic resonance imaging (fMRI) for clinical neuroscience research in MS. Environment and Career Development Plan: Dartmouth has well-established, NIH/NSF-sponsored research programs and facilities related to the Candidate's proposed career development program. These include the Brain Imaging Laboratory, the Dartmouth Experimental Visualization Laboratory of the Computer Science Department, and the Dartmouth MS Center. The directors of each of these laboratories are mentors on the project, and other scientists will contribute in their respective areas of expertise in imaging and MS. The Candidate will spend 70% of her time in hands-on training in the Brain Imaging Laboratory. The remaining time will be divided among the MS Center, other mentors, didactics, and training in research ethics. Research Plan: Recent advances in MRI research have lead to the discovery of previously unrecognized diffuse brain abnormalities in MS, as well as increased possibly compensatory brain activity that may help diminish the impact of disease on daily functioning. The Specific Aims of the project are: 1) to compare brain activity in patients and controls during performance of cognitive and motor tasks;2) to relate changes in cerebral activity to MS-related damage within and outside the circuitry normally associated with specific cognitive and motor functions;and 3) to relate changes in cerebral activation to level of ability to perform motor and cognitive functions. The proposed project is a controlled, cross-sectional study using fMRI, structural MRI, and neuropsychological testing in 60 patients with MS and 30 healthy controls. This project will advance understanding of relations between MRI findings and symptoms in MS, and ultimately inform and improve the clinical management of MS and other diseases.